Natural Product Isolation and Function Identification

The symbiosis between the plant Psychotria kirkii and the leaf nodule bacteria Burkholderia kirkii is crucial to the survival of both species. In order to investigate the chemical nature of this symbiosis we identified a gene cluster in B. kirkii that appeared to code for a C7 aminocyclitol secondary metabolite. Isolation and charicterisation of this metabolite revealed the novel aminocyclitol kirkamide. As the quantity of kirkamide available from isolation was very small we used total synthesis to obtain large quantities of material for biological evaluation. Kirkamide showed toxicity to crustaceans and insects indicating that it is possibly plays a protective role in the symbiosis.

Cyanobacteria are a relatively unexplored source of novel natural products. We screened cyanobacterial extracts in a telomerase inhibitor assay and then used bioassay guided fractionation to identify the active compounds. These were found to be a series of sulfoqunovosyl diacylglycerols (SQDGs) functionalised with a mixture of different fatty acid chains. We prepared pure SQDG’s by chemical synthesis and determined that the bis-palmitoyl substituted SQDG inhibits telomerase with an IC50 of 17 mM. We were ableto use our synthetic route to prepare analogues for SAR studies and determine the influence of the fatty acid substituent on the telomerase inhibitory activity.